We have constructed a cell line for expressing human APP and PSI proteins using mouse neuroplastorna cells (N2a cell) and studied the effect of PSI mutations on AP production by analyzing AP peptide composition in cell culture media conditioned by cells transfected with human APP and PSI cDNAs. We have also studied the effect of PSI mutations on AP degradation by analyzing proteolytic degradation products of synthetic AP peptide (API-40 and API-42) in cultured cells transfectes with wildtype and mutant human PSI cDNAs. Finally, we are analyzing AP peptides in human cerebrospinal. fluid (CSF) and brain tissue specimens of AD patient with PSI mutations to determine whether we can determine abnon-nal pattern and levels in patients with disease.